Fig. 7
Gata3-deficient tumor cells are sensitive to PARPi and reconstitution of Gata3 de-sensitizes Brca1-deficient cells to PARPi. a MMTV-PyMT (Gata3+/+;Brca1+/+), p18−/−;Gata3+/− (Gata3+/−), and p18−/−;Brca1+/− (Brca1+/−) mammary tumor cells were treated with DMSO or OLA at 10 μM. Forty-eight hours later, the cell number was counted. b, c Gata3+/+;Brca1+/+ mammary tumor cells infected with psi-LVRU6GP-control (sh-Ctrl) or psi-LVRU6GP-Gata3 (sh-Gata3), selected with puromycin, and analyzed for Gata3 expression (b). Gata3+/+;Brca1+/+-sh-Ctrl and Gata3+/+;Brca1+/+-sh-Gata3 cells in b were treated with DMSO or OLA for 48 h; the cell number was counted (c). d, e p18−/−;Brca1+/− (Brca1+/−) mammary tumor cells infected with pLVX-Flag (Empty) or pLVX-Flag-Gata3 (Gata3), selected with hygromycin, and analyzed for Gata3 expression (d). Empty- and Gata3-expressing Brca1+/− cells in (d) were treated with DMSO or OLA for 48 h; the cell number was counted (e). Data in a, c, and e represent the mean ± SD from duplicates of three independent experiments. The asterisk (*) denotes a statistical significance from DMSO- and OLA-treated samples determined by the T-test. The number sign (#) denotes a statistical insignificance from DMSO- and OLA-treated samples determined by the T-test. f–h MMTV-PyMT (Gata3+/+;Brca1+/+), p18−/−;Gata3+/− (Gata3+/−), and p18−/−;Brca1+/− (Brca1+/−) tumor cells (f), Gata3+/+;Brca1+/+ tumor cells infected with sh-Ctrl or sh-Gata3 (g), or p18−/−;Brca1+/− (Brca1+/−) tumor cells infected with pLVX-Flag (Empty) or pLVX-Flag-Gata3 (Gata3) (h) were treated with DMSO or OLA (1 μM) and analyzed by clonogenic assay. Data represent the mean ± SD from triplicates of two independent experiments. The asterisk (*) denotes a statistical significance from DMSO- and OLA-treated samples, and the asterisk (**) denotes a statistical significance from Flag and Gata3 samples treated with OLA. The number sign (#) denotes a statistical insignificance from DMSO- and OLA-treated samples determined by the T-test